The skin epidermis plays a role in protecting the inside of the skin from bacteria, viruses, ultraviolet rays, chemical substances and the like. In the epidermis, keratinocytes undergo keratinization and cell death to form the stratum corneum, while other keratinocytes are grown and differentiated repeatedly. Afterwards, the stratum corneum turns into dirt and is exfoliated from the epidermis. Typically, this cycle (turnover) over about 28 days is repeated. However, in skin diseases such as skin cancer, psoriasis, immunologic/allergic skin diseases and chronic wound, it is observed that the control mechanism for the cell proliferation of keratinocytes breaks down and the skin is thickened by the abnormal proliferation of skin epithelial cells (Non Patent Document 1).
Steroid formulations have conventionally been used for therapy of psoriasis. Steroid formulations are active in inhibiting inflammation and in suppressing the immune function and are also highly therapeutically effective. However, it is known that everyday use of steroid formulations causes various side effects such as skin atrophy and skin thinning.
Recently, several compounds have been reported which inhibit the proliferation of keratinocytes. For example, active vitamin D3 or derivatives thereof have been reported to inhibit the proliferation of keratinocytes and to be effective for psoriasis and keratosis (Patent Documents 1 and 2 and Non Patent Document 2). Zearalenone derivatives (Patent Document 3), azasugar derivatives (Patent Document 4), hydroxamic acid derivatives (Patent Document 5) and phosphodiester compounds with ascorbic acid and tocopherol (Patent Document 6) have also been reported to inhibit the proliferation of keratinocytes.
DHODH inhibitors have also been reported as other compounds to inhibit the proliferation of keratinocytes (Patent Documents 7 and 8).